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• Newly diagnosed patients with histologically proven ALCL (International
Classification of Diseases for Oncology [ICD-0] code: 9714/3)
• Disease must be cluster of differentiation (CD)30 positive
• Disease must be anaplastic lymphoma kinase (ALK) positive (defined by local
institutional standards)
• Patients must have stage II, III, or IV disease
• Patients must have a life expectancy of >= 8 weeks
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x
upper limit of normal (ULN) for age; for the purpose of this study, the ULN for ALT
is 45 U/L
• If the lab abnormality is thought to be due to the lymphoma the patient is eligible
and dose adjustments should be made
• Shortening fraction of >= 27% by echocardiogram, or
• Ejection fraction of >= 50% by radionuclide angiogram
• Patients with a history of pulmonary dysfunction must have no evidence of dyspnea at
rest, no exercise intolerance due to pulmonary insufficiency, and a pulse oximetry >
92% while breathing room air unless current dysfunction is due to the lymphoma in
which case the patient is eligible

Exclusion Criteria:

• Patients with central nervous system (CNS) disease are not eligible
• Patients with disease limited to the skin are not eligible, regardless of how
wide-spread
• Patients with stage I disease are not eligible
• Patients who have received any prior cytotoxic chemotherapy for the current diagnosis
of ALCL or any cancer diagnosed previously are not eligible
• Previous steroid treatment and/or radiation treatment is not allowed unless it is for
the emergent management of a mediastinal mass; emergent steroid treatment and/or
radiation treatment should stop once protocol therapy is initiated
• Intrathecal chemotherapy prior to enrollment is allowed for the current diagnosis of
ALCL as long as adequate cerebrospinal fluid (CSF) is obtained prior to
administration of the intrathecal chemotherapy and subsequently demonstrated to be
negative for ALCL
• Female patients who are pregnant are not eligible; pregnancy tests must be obtained
in girls who are post menarchal
• Lactating females are not eligible unless they have agreed not to breastfeed their
infants
• Sexually active patients of reproductive potential are not eligible unless they agree
to use an effective contraceptive method for the duration of treatment and for 3
months after stopping treatment
• Patients with Down syndrome are not eligible
• Patients with an immunodeficiency that existed prior to diagnosis such as primary
immunodeficiency syndromes or organ transplant recipients are not eligible
• Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates with narrow
therapeutic indices: Patients chronically receiving medications known to be
metabolized by CYP3A4 and with narrow therapeutic indices including pimozide,
aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical
use of these medications (if applicable) is allowed
• CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4
inhibitors within 7 days prior to study enrollment, including but not limited to
ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir,
nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit
juice are not eligible; the topical use of these medications (if applicable), e.g. 2%
ketoconazole cream, is allowed
• CYP3A4 inducers: patients chronically receiving drugs that are known potent CYP3A4
inducers within 12 days prior to study enrollment, including but not limited to
carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, ritonavir, and St.
John's wort are not eligible; the topical use of these medications (if applicable) is
allowed
• Patients that are known to be positive for human immunodeficiency virus (HIV) are not
eligible; note: inclusion of HIV positive patients will be considered at a later date
• Patients who weigh < 10 kg are not eligible

• Patients must be enrolled on AALL08B1 prior to enrollment on AALL1131
• White Blood Cell Count (WBC) Criteria
• Age 1-9.99 years: WBC >= 50 000/uL
• Age 10-30.99 years: Any WBC
• Age 1-30.99 years: Any WBC with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment
• Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health
Organization [WHO] classification) (also termed B-precursor acute lymphoblastic
leukemia); patients with Down syndrome are also eligible
• Eligibility criteria for the Incidence and Natural History of Osteonecrosis study
• Patients must be 10 years of age or greater at the time of B-ALL diagnosis,
enrolled on AALL1131
• Patients with Down syndrome are not eligible
• Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive
Functioning study
• Patients must be aged 6 to 11 years at time of B-ALL diagnosis, enrolled on
AALL1131
• Patients must be English-, French- or Spanish-speaking (languages in which the
assessment is available)
• Patients must have no known history of neurodevelopmental disorder prior to
diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental
retardation)
• Patients must have no significant visual impairment that would prevent computer
use and recognition of the visual test stimuli
• Eligibility criteria for the National Cancer Institute (NCI) standard risk patients
from AALL0932 enrolling on this study at the end of Induction:
• Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR
B-ALL stratum of this study at the end of Induction:
• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with
day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 BM
MRD < 0.01%
• With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day
8 PB MRD and day 29 bone marrow (BM) MRD >= 0.01%
• Both NCI standard risk (SR) and HR patients without Down syndrome and with
testicular disease at diagnosis, who do not meet other VHR criteria, will be
eligible for the HR stratum
• Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the
VHR B-ALL stratum of this study at the end of Induction:
• Intrachromosomal amplification of chromosome 21 (iAMP21)
• Mixed-lineage leukemia (MLL) rearrangement
• Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index <
0.81)
• Induction failure (M3 BM at day 29)
• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with
day 29 BM MRD >= 0.01%
• Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria
will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS
HR B-ALL stratum of this study at the end of Induction:
• Day 29 MRD >= 0.01%
• MLL rearrangement
• Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
• DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction
failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for
post-Induction therapy on either trial (AALL0932 or AALL1131)
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human
studies must be met

Exclusion Criteria:

• With the exception of steroid pretreatment or the administration of intrathecal
cytarabine, patients must not have received any prior cytotoxic chemotherapy for
either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation
of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed
after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving
prior steroid therapy may be eligible for AALL1131
• Patients with breakpoint cluster region (BCR)-v-abl Abelson murine leukemia viral
oncogene homolog 1 (ABL1) fusion (not eligible for post-Induction therapy on this
study; non-DS patients may be eligible to enroll in AALL1122 or successor Children's
Oncology Group [COG] Philadelphia positive [Ph+] ALL trial by day 15 Induction)
• DS HR B-ALL patients with Induction failure or BCR-ABL1
• Female patients who are pregnant are ineligible
• Lactating females are not eligible unless they have agreed not to breastfeed their
infant
• Female patients of childbearing potential are not eligible unless a negative
pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation

• Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing
sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible
for this study; note:
• For the purpose of this study, chest wall tumors with ipsilateral pleural
effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural
based secondary tumor nodules will be considered localized disease
• Patients with regional node involvement, based on clinical suspicion confirmed
by pathologic documentation are considered to be non-metastatic
• Patients with discontinuous osseous lesions within the same bone are considered
to be non-metastatic
• Tumors arising in the bony skull (extra-dural) are considered to be extracranial
• Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by
institutional pathologist
• No prior chemotherapy or radiation therapy is allowed; patients should only have had
a biopsy of the primary tumor without an attempt at complete or partial resection;
patients will still be eligible if unplanned excision was attempted or accomplished
as long as adequate imaging was obtained prior to surgery
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >=
70mL/min/1.73 m^2 or serum creatinine based on age/gender as follows:
• 1 month to < 6 months: 0.4 mg/dL
• 6 months to < 1 year: 0.5 mg/dL
• 1 to < 2 years: 0.6 mg/dL
• 2 to < 6 years: 0.8 mg/dL
• 6 to < 10 years: 1 mg/dL
• 10 to < 13 years: 1.2 mg/dL
• 13 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)
• Total bilirubin < 1.5 x upper limit of normal (ULN) for age
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram

Exclusion Criteria:

• Patients must have no evidence of metastatic disease; metastatic disease:
• Are lesions which are discontinuous from the primary tumor, are not regional
lymph nodes and do not share a body cavity with the primary tumor; if there is
any doubt whether lesions are metastatic, a biopsy of those lesions should be
taken
• Skeletal lesions in adjacent bones (trans-articular)
• Contralateral pleural effusion and contralateral pleural nodules
• Distant lymph node involvement
• Patients with pulmonary nodules are considered to have metastatic disease if the
patient has:
• Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied
and negative for Ewing's
• Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not
required but if performed and positive indicate metastatic disease
• Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium
and spine are not eligible
• Patients with pathologic diagnoses other than Ewing sarcoma will be excluded
• Patients diagnosed with Ewing Sarcoma as a second malignant neoplasm are not eligible
if they have received chemotherapy or radiation for the treatment of their primary
malignancy
• Pregnant women will not be entered on this study; pregnancy tests must be obtained in
female patients who are post-menarchal; lactating females may not participate unless
they have agreed not to breastfeed their infants; males or females of reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of the study treatment
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
up to to 30 year(s) old

Phase:
N/A

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• All newly diagnosed patients with suspected neuroblastoma, suspected
ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's
Oncology Group (COG) institutions are eligible for this study
• There will be no penalty under any circumstances for enrollment of a patient
whose definitive institutional diagnosis, or central review diagnosis, is found
to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/
maturing subtype
• Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and
procurement of study-related tissues with the following exception:
• Patients that in the opinion of the treating physician are too ill to undergo
pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on
ANBL00B1; documentation of the emergent nature of therapy initiation is required
• It is required that a good faith effort (documented by specimen tracking) be made to
submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow)
of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in
order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be
obtained prior to initiation of therapy
• Exceptions
• In rare cases, patients may be deemed too ill to undergo pre-treatment tissue
biopsy and require EMERGENT therapy; the following eligibility guidelines apply
to these cases:
• For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g.,
primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT
therapy initiation should be made; however, if the child is deemed too
unstable for such a procedure they may still be enrolled as long as
pre-treatment peripheral blood and serum have been submitted
• For all other INSS stages: tumor tissue should be obtained as soon as
possible within 96 hours of EMERGENT therapy initiation; patients without
tumor tissues submitted within this time-frame are not eligible for
enrollment
• Note: it may not be possible to obtain all necessary tumor biomarkers
for therapy stratification in such cases; if a patient enrolled on
ANBL00B1 undergoes an additional diagnostic procedure within 96 hours
of initiating therapy, additional tumor specimens may be submitted to
obtain biomarkers used for risk classification; the decision to
perform such procedures, and/or submit these specimens, is to be made
by the managing clinicians and should reflect the clinical need to
know the status of such biomarkers
• Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a
tumor biopsy or resection upfront; tumor tissue submission is therefore not
required for these patients to enroll on ANBL00B1; a peripheral blood and
serum sample is the only specimen required to be submitted for this group
of patients; should they undergo a biopsy or resection at a later date
tumor can be submitted for biomarker testing at this time
• All patients and/or their parents or legal guardians must sign a written informed
consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Exclusion Criteria:

• Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original
diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1
protocol

Selinexor (KPT-330) in Older Patients With Relapsed AML (SOPRA)

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
60 and over

Phase:
Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Age = 60 years with relapsed/refractory AML of any type except for acute
promyelocytic leukemia (APL; AML M3), after at least 1 prior AML therapy , who have
never undergone, and who are not currently eligible for, stem cell transplantation,
and are currently deemed unfit for intensive chemotherapy.
• ECOG = 2.
• Must have available archival or recently acquired bone marrow biopsy/aspiration or
tumor tissue for central review to be eligible.
• Relapsed or refractory AML, defined as either: recurrence of disease after a complete
remission (CR), or failure to achieve CR with initial therapy.
• Must have received at least 1 prior line of AML therapy given at standard doses and
must have progressed after their most recent therapy. Prior therapy must have
included: a hypomethylating agent with at least 2 cycles.
• At least 2 weeks must have elapsed since the last anti-leukemia treatment (with the
exception of hydroxyurea) before first dose in this study.

Exclusion Criteria:

• Treatment with any investigational agent within 3 weeks prior to first dose in this
study.
• Presence of central nervous system (CNS) leukemia.
• In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic
syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML
therapy.
• Major surgery within 2 weeks of first dose of study drug. Patients must have
recovered from the effects of any surgery performed greater than 2 weeks previously.
• Concurrent active malignancy under treatment.
• Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be
positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).
• Known HIV infection.
• Unable to swallow tablets, or patients with malabsorption syndrome, or any other
disease significantly affecting gastrointestinal function.
• Patients whose AML is classified as favorable according to the European LeukemiaNet
(ELN) disease risk assessment.

MRI and Gene Expression in Diagnosing Patients With Ductal Breast Cancer In Situ

Contact(s):
Susann E. Schetter -CTO@hmc.psu.edu

Gender:
Female

Age:
18 and over

Phase:
N/A

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Registration to Step 1:
• Patients must have pathologically confirmed diagnosis of unilateral ductal carcinoma
in situ with no evidence of microinvasive or invasive disease obtained by core needle
biopsy within 4 months of registration; patients diagnosed by surgical excision are
not eligible; patients with synchronous bilateral disease are not eligible; patients
with synchronous bilateral disease (i.e., synchronous DCIS or invasive cancer) are
not eligible
• Patients will be staged prior to registration according to the clinical staging
criteria adapted from the American Joint Committee on Cancer (AJCC) Cancer
Staging Data Forms of the AJCC Cancer Staging Manual, 7th Edition, 2009; Note:
For consistency purposes, AJCC 7th Edition will continue to be used throughout
the entire study enrollment period
• Required studies include a bilateral screening mammogram within 6 months and
diagnostic mammogram of the affected breast within 3 months prior to registration
• Patients must not have previous ipsilateral invasive breast cancer or DCIS
• Patients must not have known deleterious mutations in breast cancer (BRCA) genes
• Patients must not have received hormonal therapy (i.e., tamoxifen, raloxifene, and/or
aromatase inhibitors) for prevention of breast cancer within 3 months of the biopsy
documenting DCIS
• Patients must not have history of chemotherapy for cancer within 6 months prior to
registration
• No prior history of breast radiotherapy that will prevent the use of radiotherapy for
the present DCIS
• Patients must be judged to be suitable to undergo MRI and receive the contrast agent
gadolinium (exclusions follow):
• No history of untreatable claustrophobia;
• No presence of metallic objects or implanted medical devices in body (i.e.,
cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial
hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the
eye, or steel implants);
• No history of sickle cell disease;
• No contraindication to intravenous contrast administration;
• No known allergy-like reaction to gadolinium or moderate or severe allergic
reactions to one or more allergens as defined by the American College of
Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as
defined by the institution's policy and/or ACR guidance;
• No findings consistent with renal failure, as determined by glomerular
filtration rate (GFR) < 30 mL/min/1.73 m^2 based on a serum creatinine level
obtained within 28 days prior to registration;
• Weight lower than that allowable by the MRI table;
• No prior MRI of the breasts within the 6 months prior to registration
• Patients must be eligible for breast-conserving therapy (BCT) based on clinical
examination and mammography; if ultrasound is performed, findings must also be
consistent with eligibility for BCT
• Patients must not have multicentric disease scheduled to undergo multiple
lumpectomies; multifocal disease that can be encompassed in a single operative bed
are eligible
• Women must not be pregnant or breast-feeding; all females of childbearing potential
must have a blood test or urine study within 3 weeks prior to registration to rule
out pregnancy; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential must be strongly advised to use an accepted and
effective method of contraception or to abstain from sexual intercourse for the
duration of their participation in the study
• Registration to Step 2:
• MRI has been performed in Step 1, and additional imaging studies and biopsies
performed if indicated
• The clinician/patient has made the decision as to whether the patient will proceed to
wide local excision or mastectomy
• Registration to Step 3:
• Patient's most recent surgery was wide local excision with or without re-excision and
for which there was obtained clear (>= 2 mm) margins at breast conserving surgery,
and the pathology reveals pure DCIS; patients with invasive cancer or DCIS with
microinvasion will not be registered on step 3, but will be followed for clinical
outcomes
• The OncotypeDX Patient Report of the DCIS Score from the OncotypeDX Breast Cancer
Assay performed by Genomic Health on the excision tissue have been uploaded by the
site into the Rave electronic case report forms (eCRF)

• PATIENT PRE-REGISTRATION ELIGIBILITY CRITERIA:
• For pre-surgical patients
• Suspected diagnosis of resectable non-small cell lung cancer; patients with
squamous cell carcinoma are eligible only if the registering site has EA5142
institutional review board (IRB) approved
• Suspected clinical stage of IIIA, II or large IB (defined as size >= 4cm)
• For post-surgical patients
• Completely resected non-small cell lung cancer; patients with squamous cell
carcinoma are eligible only if the registering site has EA5142 IRB approved
• Pathologic stage IIIA, II or IB (defined as size >= 4 cm)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• No patients who have received neoadjuvant therapy (chemo- or radio-therapy) for this
lung cancer
• No prior or concurrent malignancies within 5 years, except non-melanoma skin
carcinoma or in situ carcinomas; a secondary primary lung cancer is considered a
concurrent malignancy and would make a patient ineligible for A151216
• No prior treatment with agents targeting EGFR mutation, ALK rearrangement, and
PD-1/PD-L1/CTLA-4
• No patients known to be pregnant or lactating
• Patients who have had local genotyping are eligible, regardless of the local result
• No patients with recurrence of lung cancer after prior resection
• Note: Post-surgical patients should proceed to registration immediately following
preregistration
• PATIENT REGISTRATION ELIGIBILITY CRITERIA:
• Completely resected NSCLC; patients with squamous cell carcinoma are eligible only if
the registering site has EA5142 IRB approved
• Pathologic stage IIIA, II, or large IB (defined as size >= 4 cm)
• Tissue available for the required analyses
• In order to allow for time for central genotyping and eligibility for the ALCHEMIST
treatment trial, patients must register within the following eligibility windows,
depending on the adjuvant treatment approach:
• If no adjuvant therapy, register patient within 75 days following surgery
• If adjuvant chemotherapy only, register patient within 225 days following
surgery
• If adjuvant chemotherapy and radiation, register patient within 285 days
following surgery

1. Radiosurgery including Gamma Knife, linear accelerator based radiosurgery, CyberKnife
and placement of Gliadel wafer
2. Presence of any other active malignancy or prior history of malignancy, except for:
basal cell carcinoma of the skin, cervical carcinoma in situ, early stage prostate
carcinoma not requiring active treatment
3. New York Heart Association >/= Grade 3 congestive heart failure within 6 months prior
to study entry
4. Uncontrolled or significant cardiovascular disease, including:
• Myocardial infarction and transient ischemic attack or stroke within 6 months
prior to enrollment
• Uncontrolled angina within 6 months
• Diagnosed or suspected congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as
ventricular tachycardia, ventricular fibrillation, or Torsades de pointes);
• Clinically significant abnormality on electrocardiogram (ECG)
5. Pulmonary disease including or greater than grade 2 dyspnea or laryngeal edema, grade
3 pulmonary edema or pulmonary hypertension according to CTCAE 4.03
6. Severe acute or chronic medical or psychiatric condition that could increase the risk
associated with trial participation or trial drug administration or could interfere
with the interpretation of trial results and, in the judgment of the investigator,
would make the patient inappropriate for entry into the trial. This includes but is
not limited to the following:
1. Immunosuppressive disease
2. Chronic renal disease / failure
3. Concurrent neurodegenerative disease,
4. Dementia or significantly altered mental status that would prohibit the
understanding or rendering of informed consent and compliance with the
requirements of the protocol.
7. Presence of an acute infection requiring active treatment with
antibiotics/antivirals; prophylactic administration is allowed
8. Known history of an autoimmune disorder
9. Known human immunodeficiency virus positivity or acquired immunodeficiency syndrome
related illness or other serious medical condition
10. Breastfeeding
11. Received any other therapeutic investigational agent within 30 days of screening,
except for immunotherapy. Patients with previous immunotherapy are not eligible
regardless of timing.
12. Contraindication to MRI
13. Foreseeable condition which would preclude the reduction of steroids (dexamethasone)
to a maximum of 2 mg BID within a week prior to apheresis -

Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
18 and over

Phase:
Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Patient must have histologically or pathologically confirmed locally unresectable or
metastatic low or intermediate grade pancreatic neuroendocrine tumor, excluding small
cell carcinoma
• Patient must have measurable disease by Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1 criteria; baseline measurements and evaluations of all sites of disease
must be obtained =< 4 weeks prior to randomization and must be acquired by
multiphasic CT or contrast magnetic resonance imaging (MRI)
• Date of last documented disease progression must be =< 12 months from date of
randomization
• Patient must not have received prior temozolomide, dacarbazine (DTIC), or
capecitabine, or 5-FU (fluorouracil) therapy
• Prior everolimus and/or sunitinib therapy is allowed, so long as it was discontinued
>= 4 weeks prior to randomization
• Concurrent somatostatin analogues are allowed provided that patients
• Have been on stable doses for 8 weeks and
• Have documented disease progression on that dose
• Patients may not be receiving any other investigational agents while on study
treatment
• Patients may not be receiving Coumadin while on treatment; other anticoagulants are
allowed
• Leukocytes >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mm^3
• Total bilirubin =< institutional upper limit of normal (ULN) or =< 1.5 X
institutional ULN (if the patient has liver metastases)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 X institutional ULN or (=< 5 X institutional ULN if the patient has liver
metastases)
• Serum creatinine =< 1.5 X institutional ULN
• Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have life expectancy >= 12 weeks
• Patients with either clinically apparent central nervous system metastases or
carcinomatous meningitis are ineligible
• Patients must NOT have active or uncontrolled infection or serious medical or
psychiatric illness
• Patients must NOT have history of allergic reactions attributed to compounds of
similar chemical or biologic composition to temozolomide or capecitabine
• Patient must NOT have absorption issues that would limit the ability to absorb study
agents
• Patients with a history of the following within =< 12 months of study entry are not
eligible:
• Arterial thromboembolic events
• Unstable angina
• Myocardial Infarction
• Patients with symptomatic peripheral vascular disease are not eligible
• Patients must NOT have previous or concurrent malignancy; exceptions are made for
patients who meet any of the following conditions:
• Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ OR
• Prior malignancy completely excised or removed and patient has been continuously
disease free for > 5 years OR
• Prior malignancy cured by non-surgical modalities and patient has been
continuously disease free for > 5 years
• Women must not be pregnant or breast-feeding; all females of childbearing potential
must have a blood test or urine study within =< 2 weeks prior to randomization to
rule out pregnancy; a female of childbearing potential is any woman, regardless of
sexual orientation or whether they have undergone tubal ligation, who meets the
following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential and sexually active males must be strongly advised to
use an accepted and effective method of contraception or to abstain from sexual
intercourse for the duration of their participation in the study; should a woman
become pregnant while participating in this study, she should inform her treating
physician immediately; if a man impregnates a woman while participating in this
study, he should inform his treating physician immediately
• Patient must be able to swallow pills
• Patient must be able to tolerate CT or magnetic resonance (MR) imaging including
contrast agents as required for their treatment and the protocol

• Sexually active males must be strongly advised to use an accepted and effective
method of contraception
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< grade 1
• Total bilirubin =< grade 1
• Note: If total bilirubin is 2 to 3 mg/dL, but direct bilirubin is normal, then
the patient will be considered eligible
• Patient must not have a concurrent active malignancy for which they are receiving
treatment (other than myelodysplastic syndromes [MDS])
• Patient must not have an active, uncontrolled infection
• ADDITIONAL INDUCTION ELIGIBILITY CRITERIA:
• Newly-diagnosed AML patients according to World Health Organization (WHO)
classification who are considered candidates for intensive chemotherapy based upon
examination of peripheral blood or bone marrow aspirate specimens or touch
preparations of the bone marrow biopsy obtained within two weeks prior to
randomization; a bone marrow aspirate is required for enrollment; however, on
occasion there is discordance between percentage of myeloblasts on the differential
of the peripheral blood or aspirate; the peripheral blood criteria are sufficient for
diagnosis; confirmatory immunophenotyping will be performed centrally
• NOTE: patients must be registered to E3903 (Ancillary Laboratory Protocol for
the Collection of Diagnostic Material on Patients Considered for Eastern
Cooperative Oncology Group (ECOG) Treatment Trials for Leukemia or Related
Hematologic Disorders) and must undergo eligibility testing for the study by
multiparameter flow cytometry
• NOTE: Southwest Oncology Group (SWOG)/Cancer Trials Support Unit (CTSU)
institutions: E3903 is not open at the CTSU; therefore, baseline submissions
must be submitted on E2906
• ECOG performance status (PS) 0-3 (restricted to ECOG PS 0-2 if >= 70 years of age)
• Patients with acute promyelocytic leukemia (APL) confirmed either by the presence of
t(15;17)(q22;q21) or promyelocytic leukemia (PML)/retinoic acid receptor (RAR) alpha
transcripts will be excluded
• Patients must not have blastic transformation of chronic myelogenous leukemia
• Patients with secondary AML are eligible for enrollment onto the trial; secondary AML
is defined as AML that has developed in a person with a history of antecedent blood
count abnormalities, or myelodysplastic syndrome (MDS), or a myeloproliferative
disorder (excluding chronic myeloid leukemia); or a history of prior chemotherapy or
radiation therapy for a disease other than AML
• NOTE: Prior therapy of MDS with decitabine, low-dose cytarabine, or azacitidine
is excluded
• Patients may not have received prior chemotherapy for AML with the exception of
hydroxyurea for increased blast count or leukapheresis for leukocytosis
• Total serum bilirubin =< 1.5 times upper limit of normal (ULN) (=< grade 1); if total
bilirubin is 2 to 3 mg/dL, but direct bilirubin is normal, then the patient will be
considered eligible
• Patients with a serum creatinine > 1 are eligible if they have a calculated
glomerular filtration rate (GFR) of >= 60 ml/min (i.e. class I or class II chronic
kidney disease ) using the Modification of Diet in Renal Disease (MDRD) formula
• Note: Daily creatinine and MDRD formula are only for the 1st induction cycle
• Cardiac ejection fraction >= 45% or within institutional normal limits; a nuclear
medicine gated blood pool examination is preferred; a two-dimensional (2-D)
echocardiogram (ECHO) scan is acceptable if a calculated ejection fraction is
obtained and follow-up measurement of the cardiac ejection fraction will also be
performed by echocardiography; measurement of cardiac ejection fraction should be
within two weeks prior to receiving treatment
• NOTE: when a multi gated acquisition scan (MUGA) or echocardiogram cannot be
obtained due to weekend or holiday, then patients may be enrolled provided there
is no history of significant cardiovascular disease and a measurement of cardiac
ejection fraction will be performed within 5 days of study enrollment
• Patients with suspected central nervous system (CNS) involvement should undergo
lumbar puncture; those with documented CNS involvement will be excluded
• Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if
adequate number of circulating blasts (>10^9/l) from peripheral blood; this must be
done via E3903
• NOTE: SWOG/CTSU institutions: E3903 is not open at the CTSU; therefore, baseline
submissions must be submitted on E2906
• Patients who have received previous treatment for antecedent hematological disorders
(AHD) with 5-azacitidine, decitabine, or low dose cytarabine will be excluded
• Patients with known human immunodeficiency virus (HIV) infection are excluded
• HLA typing should be performed at registration, if possible
• Diagnostic bone marrow and peripheral blood specimens must be submitted for
immunophenotyping and selected molecular testing; this must be done via E2906
• NOTE: SWOG/CTSU institutions: E3903 is not open at the CTSU; therefore, baseline
submissions must be submitted on E2906
• CONSOLIDATION CRITERIA:
• NOTE: All patients achieving CR or complete remission with incomplete blood count
recovery (CRi) will receive consolidation when fit
• NOTE: Patients proceeding to transplant are allowed up to one cycle of consolidation
treatment
• Consolidation cycle 1 must commence within sixty days of the bone marrow aspirate and
biopsy that confirmed the presence of a CR or CRi
• Patients must have achieved a CR or CRi (or morphologic leukemia-free state for those
patients proceeding to Arm G transplant)
• Patients who have achieved a CR or CRi must have maintained peripheral blood evidence
of a CR or CRi
• Patients must have an ECOG performance status of 0-2
• Patients must have resolved any serious infectious complications related to induction
• NOTE: Patients with an HLA-matched donor and proceeding to transplant will be
allowed up to one cycle of consolidation treatment
• Any significant medical complications related to induction must have resolved
• Patients must have a creatinine and AST =< grade 1
• MAINTENANCE CRITERIA:
• Maintenance should commence within 60 days of recovery of peripheral blood counts
after consolidation cycle 2; patients must begin consolidation cycle 2 within 60 days
of recovery to be eligible for further therapy
• Patients must have maintained peripheral blood evidence of a remission and must have
a CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy and
cytogenetic analysis
• Patients must have an ECOG performance status of 0 -2
• Patients must have resolved any serious infectious complications related to
consolidation cycle 2
• Any significant medical complications related to consolidation cycle 2 must have
resolved
• Total serum bilirubin =< 1.5 x ULN
• NOTE: if total bilirubin is 2-3 mg/dL, but direct bilirubin is normal, then the
patient will be considered eligible
• Serum creatinine =< grade 1
• The absolute neutrophil count (ANC) must be > 1000 mm^3 prior to starting every cycle
of treatment with decitabine; decitabine may be delayed for up to 4 weeks between
cycles (i.e. may be administered as infrequently as every (q) 8 weeks) while waiting
for counts to recover
• The platelet count must be > 75,000 mm^3 prior to starting every cycle of treatment
with decitabine; decitabine may be delayed for up to 4 weeks between cycles (i.e. may
be administered as infrequently as every (q) 8 weeks) while waiting for counts to
recover
• ALLOGENEIC TRANSPLANTATION:
• Patients must be > 30 days and < 90 days from the start of induction or re-induction
chemotherapy, or > 30 days and < 90 days of recovery from consolidation cycle 1 (if
received), and must have achieved a response to induction therapy (CR, CRi, or
"morphologic disease-free state", documented > 27 days after start of most-recent
chemotherapy)
• Patients must have recovered from the effects of induction, re-induction, or
consolidation chemotherapy (all toxicities =< grade I with the exception of
reversible electrolyte abnormalities), and have no ongoing active infection requiring
treatment
• Patients must have a total serum bilirubin =< 1.5 x ULN (grade =< 1) and a serum
creatinine =< grade 1
• An eligible HLA-identical donor (either related or unrelated) should be available; in
sibling donors, low resolution HLA typing (A,B,DR) will be considered sufficient; in
the case of unrelated donors, high-resolution class I and II typing (A, B, C, DRB1
and DQ) should be matched at all 10 loci; donors must be willing and able to undergo
peripheral blood progenitor mobilization
• HLA-identical sibling (6/6): the donor must be determined to be an HLA-identical
sibling (6/6) by serologic typing for class (A, B) and low resolution molecular
typing for class II (DRB1)
• Matched unrelated donor (10/10): high resolution molecular typing at the
following loci is required: HLA-A, -B, -C, -DRBL, and -DQB1
• NOTE: for matched donors •will allow select 1 antigen mismatched sibling donors
and unrelated donors in accordance with site institutional standard, as long as
matched at HLA-A, HLA-B, HLA-C, and DRB1, and with advanced discussion/approval
by the Study Chair and the bone marrow transplant (BMT) co-chair
• Patients must be considered reliable enough to comply with the medication regimen and
follow-up, and have social support necessary to allow this compliance
• Patients must have a cardiac ejection fraction of >= 40%, or within institutional
normal limits; a nuclear medicine gated blood pool examination is preferred; a 2-D
ECHO scan is acceptable if a calculated ejection fraction is obtained and follow-up
measurement of the cardiac ejection fraction will also be performed by
echocardiography; measurement of cardiac ejection fraction should be within two weeks
prior to allogeneic transplantation
• Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary
disease
• No known hypersensitivity to Escherichia (E.) coli-derived products
• No human immunodeficiency virus (HIV) infection; patients with immune dysfunction are
at a significantly higher risk of toxicities from intensive immunosuppressive
therapies
• Creatinine =< grade 1
• Bilirubin =< grade 1
• If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be
considered eligible
• AST =< grade 1

• Patients must be diagnosed with CLL in accordance with International Workshop on
Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the
following:
• >= 5 x 10^9 B lymphocytes (5000/uL) in the peripheral blood
• On morphologic review, the leukemic cells must be small mature lymphocytes, and
prolymphocytes must not exceed 55% of the blood lymphocytes
• CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell
population, which express the B cell surface markers of cluster of
differentiation (CD)19 and CD20, as well as the T-cell antigen CD5; patients
with bright surface immunoglobulin expression or lack of CD23 expression in >
10% of cells must lack t(11;14) translocation by interphase cytogenetics
• Patients must be intermediate or high-risk Rai stage CLL
• Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus
enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly
• High risk (formerly Rai stage III/IV) is defined by fulfilling criteria for
intermediate risk disease plus disease-related anemia (hemoglobin < 11 g/dL) or
thrombocytopenia (platelet count < 100 x 10^9/L) that is not attributable to
autoimmune hemolytic anemia or thrombocytopenia
• Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which
includes at least one of the following criteria:
• Evidence of marrow failure as manifested by the development or worsening of
anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or
thrombocytopenia)
• Massive (>= 6 cm below the costal margin), progressive or symptomatic
splenomegaly
• Massive nodes (>= 10 cm) or progressive or symptomatic lymphadenopathy
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard
therapy
• Constitutional symptoms, which include any of the following:
• Unintentional weight loss of 10% or more within 6 months
• Significant fatigue
• Fevers > 100.5 degrees F for 2 weeks or more without evidence of infection
• Night sweats > 1 month without evidence of infection
• Prior treatment
• Patients must not have had prior therapy for CLL (except palliative steroids or
treatment of autoimmune complications of CLL with rituximab or steroids)
• Treatment with rituximab and/or high dose corticosteroids for autoimmune
complications of CLL must be complete at least 4 weeks prior to enrollment;
palliative steroids must be at a dose not higher than 20 mg/day of prednisone or
equivalent corticosteroid at the time of registration
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patients with active hepatitis B defined by hepatitis B surface antigen positivity or
core antibody positivity in the presence of hepatitis B DNA are not eligible for this
study; patients with a positive hepatitis B core antibody but with negative hepatitis
B DNA may participate, but must have hepatitis serologies and hepatitis B DNA
monitored periodically by the treating physician
• Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B
serology; if patients receiving routine IVIG have core antibody or surface
antigen positivity without evidence of active viremia (negative hepatitis B DNA)
they may still participate in the study, but should have hepatitis serologies
and hepatitis B DNA monitored periodically by the treating physician
• Patients must not be receiving active systemic anticoagulation with heparin or
warfarin; patients must be off warfarin therapy for at least 30 days prior to
enrollment
• Patients with class III or class IV heart failure by New York Heart Association,
those with unstable angina, and those with uncontrolled arrhythmia are not eligible
• Patients who have had a myocardial infarction, intracranial bleed, or stroke within
the past 6 months are not eligible
• Patients with human immunodeficiency virus (HIV) are eligible if their CD4 count is
>= 350 cells/mm^3 and if they are not taking prohibited cytochrome (CYP)-interacting
medications
• Patients must not have any history of Richter's transformation or prolymphocytic
leukemia (prolymphocytes in blood > 55%)
• Patients must not require more than 20 mg prednisone or equivalent corticosteroid
daily
• Patients must not have uncontrolled active systemic infection requiring intravenous
antibiotics
• Patients must not have continued requirement for therapy with a strong cytochrome
P450 3A4/5 (CYP3A4/5) inhibitor or inducer
• Patients must not have a known allergy to mannitol
• Patients must not have prior significant hypersensitivity to rituximab (not including
infusion reactions)
• Patients may not have had major surgery within 10 days of enrollment, or minor
surgery within 7 days of enrollment; examples of minor surgery include dental
surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint;
the decision about whether a surgery is major or minor can be made at the discretion
of the treating physician
• Absolute neutrophil count (ANC) >= 1,000/uL unless due to bone marrow involvement
• Aspartate aminotransferase (AST) or alanine aminotransferase (AST) =< 2.5 x upper
limits of normal except if due to disease infiltration of the liver
• Bilirubin =< 1.5 x upper limits of normal (unless due to liver involvement,
hemolysis, or Gilbert's disease)
• Creatinine clearance >= 40 mL/min
• To be calculated by modified Cockcroft-Gault formula
• Platelet count (untransfused) >= 30,000/uL

Confirmatory Study of Eteplirsen in DMD Patients (PROMOVI)

• Male 7-16 years old
• Diagnosed with DMD, genotypically confirmed
• Stable dose of corticosteroids for at least 6 months
• Have intact right and left alternative upper muscle groups
• Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters)
• Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and
LVEF of greater than 50%

Exclusion Criteria:

• Previous treatment with drisapersen or any other RNA antisense agent or any gene
therapy within the last 6 months
• Participation in any other DMD interventional clinical study within 12 weeks
• Major surgery within 3 months
• Presence of other clinically significant illness
• Major change in the physical therapy regime within 3 months
Other inclusion/exclusion criteria apply.

Pomalidomide in Combination With Low-dose Dexamethasone or Pomalidomide in Combination With Low-dose Dexamethasone and Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Following Lenalidomide-based Therapy in the First or Second Line Setting (POM MM 014)

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
18 and over

Phase:
Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

•Subjects must satisfy the following criteria to be enrolled in the study:
1. Adults (age = 18 years at the time of signing the ICD) with documented diagnosis of
MM and measurable disease (serum M-protein = 0.5 g/dL or urine M-protein = 200 mg/24
hours).
2. Subjects enrolling in Cohort A (Pom+LD-dex) must have received 2 prior treatment
lines of anti-myeloma therapy. Subjects enrolling in Cohort B (Pom+Dara+LD-dex) must
have received 1 or 2 prior treatment lines of anti-myeloma therapy.
3. All subjects must have received prior treatment with LEN or a LEN-containing regimen
for at least 2 consecutive cycles as the most recent treatment regimen.
4. All subjects must have documented disease progression during or after their last
antimyeloma therapy.
5. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0, 1, or 2.
6. Subjects must understand and voluntarily sign an ICD prior to any study related
assessments/procedures being conducted.
7. Subjects must be able to adhere to the study visit schedule and other protocol
requirements.
8. All subjects must provide an adequate bone marrow sample at screening that
definitively evaluates the presence or absence of myelodysplastic changes.
9. Females with child-bearing potential (FCBP†) must agree to use 2 reliable forms of
contraception* simultaneously or practice complete abstinence from heterosexual
contact for at least 28 days before starting study drug, while participating in the
study (including during dose interruptions), and for at least 28 days after study
treatment discontinuation and must agree to regular pregnancy testing during this
timeframe. For subjects enrolled in Cohort B, pregnancy prevention and testing will
continue until 3 months after last dose of daratumumab.
10. Females must agree to abstain from breastfeeding during study participation and 28
days after study drug discontinuation. Female subjects enrolled in Cohort B must
agree to abstain from breastfeeding and donating eggs during study participation and
until 3 months after last dose of daratumumab.
11. Males must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and for 28 days following discontinuation from this study,
even if he has undergone a successful vasectomy. Male subjects enrolled in Cohort B
must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and until 3 months after last dose of daratumumab.
12. Males must also agree to refrain from donating semen or sperm during the treatment
phase and for 28 days after discontinuation from this study treatment. Male subjects
enrolled in Cohort B must also agree to refrain from donating semen or sperm during
the treatment phase and until 3 months after last dose of daratumumab.
13. All subjects must agree to refrain from donating blood while on study therapy and for
28 days after discontinuation from this study treatment.
14. All subjects must agree not to share medication.

Exclusion Criteria:

The presence of any of the following will exclude a subject from study enrollment:
1. Any of the following laboratory abnormalities:
• Absolute neutrophil count < 1,000/µL
• Platelet count < 75,000/µL for subjects in whom < 50% of bone marrow nucleated
cells are plasma cells; or a platelet count < 30,000/µL for subjects in whom =
50% of bone marrow nucleated cells are plasma cells.
• Severe renal impairment (Creatinine Clearance [CrCl] < 30 mL/min) requiring
dialysis.
• Corrected serum calcium > 11.5 mg/dL (> 2.8 mmol/L)
• Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior red blood cell transfusion or
recombinant human erythropoietin use is permitted)
• Serum SGOT/AST or SGPT/ALT > 3.0 x the upper limit of normal (ULN)
• Serum total bilirubin > 2.0 mg/dL (34.2 µmol/L); or > 3.0 x ULN for subjects
with hereditary benign hyperbilirubinemia
2. Prior history of malignancies, other than MM, unless the subject has been free of the
disease for = 5 years. Allowed exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Incidental histological finding of prostate cancer (TNM [tumor, nodes,
metastasis] stage of T1a or T1b)
3. Previous therapy with pomalidomide or daratumumab
4. Hypersensitivity to thalidomide, LEN, or dex (this includes = Grade 3 rash during
prior thalidomide or LEN therapy)
5. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem
cell transplant less than 12 months prior to initiation of study treatment and who
have not discontinued immunosuppressive treatment for at least 4 weeks prior to
initiation of study treatment and are currently dependent on such treatment.
6. Subjects with any one of the following:
• Congestive heart failure (NY Heart Association Class III or IV)
• Myocardial infarction within 12 months prior to starting study treatment
• Unstable or poorly controlled angina pectoris, including Prinzmetal's variant
angina pectoris
7. Subjects who received any of the following within 14 days of initiation of study
treatment:
• Major surgery (kyphoplasty is not considered major surgery)
• Use of any anti-myeloma drug therapy
8. Use of any investigational agents within 28 days or 5 half-lives (whichever is
longer) of treatment, unless approved by the sponsor.
9. Incidence of gastrointestinal disease that may significantly alter the absorption of
Pomalidomide.
10. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
11. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the ICD
12. Pregnant or breastfeeding females
13. Known human immunodeficiency virus (HIV) positivity; active infectious hepatitis A,
B, or C; or chronic hepatitis B or C
14. For subjects enrolling in Cohort B •Subject has known allergies, hypersensitivity to
mannitol, corticosteroids, monoclonal antibodies or human proteins, or their
excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived
products.

1. Patient has a Glasgow Coma Scale motor score of 0-4 or a Glasgow Coma Scale motor
score of 5 with a significant traumatic brain injury (defined as an AIS code of 5 or
6) at time of consent
2. Patient has third degree burns on >10% total surface area affecting the study limb
3. Patient has a previous leg or foot amputation of either limb
4. Patient is non-ambulatory due to an associated complete spinal cord injury
5. Patient non-ambulatory pre-injury
6. Patient speaks neither English nor Spanish
7. Patient likely to have severe problems with maintaining follow- up due to at least
one of the following:
1. Patient has been diagnosed with a severe psychiatric condition
2. Patient is intellectually challenged without adequate family support
3. Patient lives outside the hospital's catchment area
4. Follow-up is planned at another medical center
5. Patients who are prisoners or homeless

Study of IDO Inhibitor in Combination With Checkpoint Inhibitors for Adult Patients With Metastatic Melanoma

Contact(s):
Becky Miller, BSN, RN, OCN -rmiller13@hmc.psu.edu

Gender:
Male or Female

Age:
18 and over

Phase:
Phase 1/Phase 2

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Unresectable Stage III or Stage IV melanoma.
• Patients must have measurable disease, defined as lesions that can be accurately
measure in in 2 perpendicular diameters with at least one diameter > 20mm and the
other >10mm on conventional CT or MRI or 10mm x 10 mm by spiral CT.
• No systemic treatment in the previous 28 days.
• Age =18 years. Because no dosing or adverse event data are currently available on the
use of ipilimumab or indoximod in patients <18 years of age, children are excluded
from this study.
• ECOG performance status =2 (Karnofsky =60% )
• Patient has adequate bone marrow and organ function as defined by the following
laboratory values :
• Absolute Neutrophil Count (ANC) = 1.0 x 109/L
• Platelets = 100 x 109/L
• Hemoglobin = 9.0 g/dL
• INR = 2 x ULN
• Potassium, calcium, magnesium = Grade 1 per CTCAE
• Serum Creatinine = 1.5 x ULN
• Serum Bilirubin, amylase and lipase = 1.5 x ULN (in patients with known Gilbert
Syndrome, total bilirubin = 3 x ULN, with direct bilirubin = 1.5 x ULN)
• AST and ALT = 3 x ULN (or = 5.0 x ULN if hepatic metastases are present)
• Serum Albumin = 3 g/dL
• Patients must have normal pituitary function as defined below:
• free T4, TSH within normal institutional limits
• ACTH within normal institutional limits
• Patients with known brain metastases will only be eligible after their tumors have
been treated with definitive resection and/or radiotherapy and they are
neurologically stable for at least 1 month off steroids.
• The effects of indoximod on the developing human fetus are unknown. For this reason
and because indoximod may affect maternal immune tolerance of the fetus, sexually
active women of child-bearing potential must agree to use two forms of contraception
(hormonal and barrier method of birth control or abstinence) prior to study entry and
for the duration of study participation. Use of contraception or abstinence should
continue for a minimum of 1 month after completion of the study. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should discontinue the study drug and inform her treating physician immediately. A
pregnancy test is required prior to study enrollment and monthly while on treatment
with indoximod for all women of child-bearing potential. Also men should be
discouraged from fathering children while on treatment.
• Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

• Patients who have had molecular targeted therapy (including vemurafenib) or
radiotherapy within 4 weeks prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients who have had prior therapy with immune checkpoint inhibition or or indoximod
are excluded from the trial. Pre-treatment with other immune modulators is allowed in
the phase 1 component of the study only. For the Phase II component, patients are
excluded if they have had prior therapy with or immune-stimulating agents including
interleukin-2, interferons, CTLA-4 or PD1 antagonists, CD40 or CD137 agonist, or
cancer therapeutic vaccines in any prior line for metastatic disease. Interferons
used in the adjuvant setting are allowed (Phase 1 or 2 component).
• Patients with known active, uncontrolled brain metastases should be excluded from
this clinical trial.
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to ipilimumab or tryptophan containing substances. This would include
L-tryptophan or 5-hydroxy-tryptophan supplements. Also patients with a history of
known hypersensitivity reactions to mouse or humanized monoclonal antibodies are
excluded.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection (especially toxoplasmosis, which could potentially be worsened by indoximod
(Divanovic et al., 2012)), symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.
• Pregnant women are excluded from this study because indoximod is an immunoregulatory
agent with the potential for abortifacient effects due to fetal rejection by the
maternal immune system. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with indoximod,
breastfeeding should be discontinued if the mother is treated with indoximod.
• Known HIV-positive patients and those with other acquired/inherited
immunodeficiencies are ineligible due the possibility of affecting the response to
indoximod, and the higher risk of active opportunistic infections.
• Any other cancer, unless the patient has been disease-free for =5 years (except
treated and cured basal-cell or squamous-cell skin cancer, superficial bladder
cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated
localized prostate cancer with undetectable PSA for 2 years).
• Patients with laboratory evidence of pancreatitis are excluded.
• Patients with autoimmune disease (e.g., psoriasis, extensive atopic dermatitis,
asthma, IBD, M.S., uveitis, vasculitis), chronic inflammatory condition, or any
condition requiring concurrent use of any systemic immunosuppressants or steroids for
any reason are excluded from the study. Patients with isolated vitiligo remain
eligible. Any patient with an allo-transplant of any kind would be excluded as well,
including xenograft heart valve. Mild, intermittent asthma requiring only occasional
beta-agonist inhaler use or mild localized eczema will not be excluded.
• Chronic use of immune-suppressive drugs (ie, systemic corticosteroids used in the
management of cancer or non-cancer related illnesses, eg, COPD).
• Patients who are receiving any other investigational agent.

• Cirrhosis with a Child-Pugh score B8-C15;
• Untreated chronic hepatitis B;
• Patients eligible for curative treatments (transplantation, surgical resection,
percutaneous treatment);
• Patients eligible for palliative treatments with demonstrated efficacy: TACE,
Sorafenib; Patients who failed to Sorafenib treatment or intolerant to sorafenib are
eligible and can be included if Sorafenib has been stopped at least 2 weeks before
randomization;
• Prior history of malignancy with the exception of adequately treated basal cell
carcinoma or in situ cervical cancer in complete remission since five years at least;
• HCC developed on transplanted liver;
• HIV infection;
• Risk of variceal bleeding;
• SaO2 < 95%;
• Presence of a significant acute or chronic respiratory disease defined as NCI/CTCAE >
grade 2;
• Presence of recent (< 6 months) or current cardiac failure (class III or IV NYHA
classification), recent (< 6 months) acute coronary syndrome, clinically significant
ECG abnormalities or recent (less than 6 months) acute vascular diseases (stroke,
MI…);
• Prior cumulative dose of 300 mg/m² of doxorubicin or equivalent;
• Patients currently treated with immunosuppressive agents that cannot be stopped;
• Patients whose medical or surgical conditions are unstable and may not allow the
study completion or compliance, and specially patients with uncontrolled diabetes;
• Uncontrolled systemic infection;
• Patients with a life expectancy of less than 2 months;
• Patients who have received an experimental drug in another clinical trial in the last
30 days prior to randomization in the present clinical trial;
• Women of child-bearing age who are unwilling or unable to use an effective
contraception method during the study treatment period and for 6 months after the
last administration of study drug, and their male partner(s) refusing to use a condom
(if applicable);
• Men who are unwilling or unable to use a condom during the study treatment period and
for 6 months after the last administration of study drug, and their female partner(s)
refusing to use one of the appropriate effective contraception methods (if
applicable);
• Patients unwilling or unable to comply with protocol requirements and scheduled
visits.

Inclusion criteria:
1. Aged between 2 and 75 years (at time of initial consent).
2. Body Mass Index (BMI) < 46 for adults (aged 16 years & older), & BMI < 28 for
children.
3. Diagnosed with primary immunodeficiency disease e.g. common variable
immunodeficiency, X-linked & autosomal forms of agammaglobulinaemia, hyper-IgM
syndrome, Wiskott-Aldrich syndrome.
4. Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and
1. IGIV dose is between 300 and 800 mg/kg/month. SCIG dose is between 110 & 300
mg/kg/week;
2. Dose is stable for at least the past three months (i.e. consistent mg/kg +/-
5%);
3. The infusion interval is every 21 or 28 days for IGIV & seven days for SCIG;
4. Has a documented trough level of = 6 g/L (600 mg/dL) on current IgG therapy. If
not available can be obtained at the screening visit, Visit 1 (Week 0).
5. Female subjects who are (or become) sexually active must practice contraception by
using a method of proven reliability for the duration of the study.
6. Females of child-bearing potential, (defined from the onset of menstruation to one
year post menopause), must have a negative result on a urine HCG-based pregnancy
test.
7. Willing to comply with all aspects of the protocol, including blood sampling, for the
duration of the study.
8. Signed an informed consent form. In the case of subjects under the legal age the
parent/guardian will sign an informed consent form & where appropriate the subject
will sign an assent form.

Exclusion Criteria:

1. Has a history of any severe anaphylactic reaction to blood or any blood-derived
product.
2. Has selective IgA deficiency or has a history of antibodies to IgA.
3. Has clinically significant impairment of cellular or innate immunity at the
discretion of the Investigator
4. Has evidence of an active infection at the time of enrolment (i.e. on day of first
infusion). Subjects who are asymptomatic but have not completed their course of
antibiotics are eligible.
5. Has previously completed or withdrawn from this study.
6. Is currently receiving, or has received, any investigational agent within the prior
three months, unless it is an investigational stage III, IIIb IGIV or SCIG.
7. Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is
nursing.
8. Is positive for any of the following at screening:
• Serological test for HIV 1&2, HCV, or HBsAg
9. Has levels at screening greater than 2.5 times the upper limit of normal as defined
at the central laboratory of any of the following:
• Alanine transaminase (ALT)
• Aspartate transaminase (AST)
10. Has severe renal impairment (defined as serum creatinine greater than two times the
upper limit of normal or BUN greater than two times the upper limit of normal for the
range of the laboratory doing the analysis); the subject is on dialysis; or has a
history of acute renal failure.
11. Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs,
or has done so within the past 12 months.
12. Has a history of DVT, or thrombotic complications of IgG therapy, or a prior
diagnosis of thrombophilia.
13. Suffers from any acute or chronic medical condition, (e.g. renal disease or
predisposing conditions for renal disease, coronary artery disease, or protein losing
state, proteinuria) that the Investigator feels may interfere with the conduct of the
study.
14. Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma,
multiple myeloma, chronic or recurrent neutropenia (ANC < 1 x 109/L).
15. Is receiving the following medication:
• Steroids (long-term daily, > 0.15 mg of prednisone equivalent/kg/day).
Requirement for short or intermittent courses of > 0.15mg/kg/day would not
exclude a subject.
• Immunosuppressive drugs
• Immunomodulatory drugs
16. If = 18 years of age, has non-controlled arterial hypertension (systolic blood
pressure > 160 mmHg &/or diastolic blood pressure > 100 mmHg). For younger subjects
refer to current guidelines for diagnosis of blood pressure1.
17. Has anemia (hemoglobin < 10 g/dL) at screening.
18. Has severe dermatitis that would preclude sites for safe product administration.

Inclusion Criteria
• Patients between the ages of 18-89 years (inclusive), in an adult ICU
• Patients admitted to the ICU who are able to communicate their pain and anxiety using
a VAS
• Patients must be cooperative and not agitated.
• Planned to have a potentially painful procedure

Exclusion Criteria:

• Diagnosed neuropathic disease
• Use of neostigmine within the past 3 hours
• Use of regional anesthesia at the extremity where the device electrodes are placed

• SCREENING/PRE-SCREENING REGISTRATION:
• Patients must have pathologically proven squamous cell carcinoma (SCCA) cancer of the
lung confirmed by tumor biopsy and/or fine-needle aspiration; disease must be stage
IV SCCA, or recurrent; the primary diagnosis of SCCA should be established using the
current World Health Organization (WHO)/International Association for the Study of
Lung Cancer (IASLC)-classification of Thoracic Malignancies; the diagnosis is based
on hematoxylin and eosin (H&E) stained slides with or without specific defined
immunohistochemistry (IHC) characteristic (p40/p63 positive, transcription
termination factor [TTF1] negative) if required for diagnosis; mixed histologies are
not allowed
• Patients must either be eligible to be screened at progression on prior treatment or
to be pre-screened prior to progression on current treatment; patients will either
consent to the screening consent or the pre-screening consent, not both; these
criteria are:
• Screening at progression on prior treatment: to be eligible for screening at
progression, patients must have received at least one line of systemic therapy
for any stage of disease (stages I-IV); at least one of these lines of therapy
must have been a platinum-based chemotherapy regimen; patients must have
progressed following the most recent line of therapy; for patients whose prior
systemic therapy was for stage I-III disease only (i.e. patient has not received
any treatment for stage IV disease), disease progression on platinum-based
chemotherapy must have occurred within one year from the last date that patient
received that therapy
• Pre-screening prior to progression on current treatment: to be eligible for
pre-screening, current treatment must be for stage IV disease and patient must
have received at least one dose of the current regimen; patients must have
previously received or currently be receiving a platinum-based chemotherapy
regimen; patients on first-line platinum-based treatment are eligible upon
receiving Cycle 1, Day 1 infusion; Note: patients will not receive their
sub-study assignment until they progress and the S1400 Notice of Progression is
submitted
• Patients must have adequate tumor tissue available, defined as >= 20% tumor cells and
>= 0.2 mm^3 tumor volume; the local interpreting pathologist must review and sign off
on the S1400 Local Pathology Review Form prior to screening/pre-screening
registration; patients must agree to have this tissue submitted to Foundation
Medicine for common broad platform Clinical Laboratory Improvement Amendments (CLIA)
biomarker profiling; if archival tumor material is exhausted, then a new fresh tumor
biopsy that is formalin-fixed and paraffin-embedded (FFPE) must be obtained; a tumor
block or FFPE slides 4-5 microns thick must be submitted; bone biopsies are not
allowed; if FFPE slides are to be submitted, at least 12 unstained slides plus an H&E
stained slide, or 13 unstained slides must be submitted; however it is strongly
recommended that 20 FFPE slides be submitted; Note: previous next-generation
deoxyribonucleic acid (DNA) sequencing (NGS) will be repeated if done outside this
study for sub-study assignment
• Patients must not have a known epidermal growth factor receptor (EGFR) mutation or
anaplastic lymphoma kinase (ALK) fusion
• Patients must have Zubrod performance status 0-1 documented within 28 days prior to
screening/pre-screening registration
• Patients must also be offered participation in banking for future use of specimens
• Patients must be willing to provide prior smoking history as required on the S1400
Onstudy Form
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines
• SUB-STUDY REGISTRATION:
• Patients whose biomarker profiling results indicate the presence of an EGFR mutation
or echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion are not
eligible
• Patients must have progressed per RECIST 1.1 following the most recent line of
therapy
• Patients must not have received any prior systemic therapy (systemic chemotherapy,
immunotherapy or investigational drug) within 21 days prior to sub-study
registration; patients must have recovered (=< grade 1) from any side effects of
prior therapy; localized palliative radiation therapy is allowed for symptom
management, provided treatment is completed >= 14 days prior to sub-study
registration; all other types of radiation must be completed >= 28 days prior to
sub-study registration
• Patients must have measurable disease documented by computed tomography (CT) or
magnetic resonance imaging (MRI); the CT from a combined positron emission tomography
(PET)/CT may be used to document only non-measurable disease unless it is of
diagnostic quality; measurable disease must be assessed within 28 days prior to
sub-study registration; pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of disease; non-measurable disease must be assessed
within 42 days prior to sub-study registration; all disease must be assessed and
documented on the Baseline Tumor Assessment Form; patients whose only measurable
disease is within a previous radiation therapy port must demonstrate clearly
progressive disease (in the opinion of the treating investigator) prior to
registration
• Patients must have a CT or MRI scan of the brain to evaluate for central nervous
system (CNS) disease within 42 days prior to sub-study registration; patient must not
have leptomeningeal disease, spinal cord compression or brain metastases unless: (1)
metastases have been locally treated and have remained clinically controlled and
asymptomatic for at least 14 days following treatment, AND (2) patient has no
residual neurological dysfunction and has been off corticosteroids for at least 1 day
prior to sub-study registration
• Patient must have fully recovered from the effects of prior surgery at least 14 days
prior to sub-study registration
• Patients must not be planning to receive any concurrent chemotherapy, immunotherapy,
biologic or hormonal therapy for cancer treatment; concurrent use of hormones for
non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement
therapy) is acceptable
• Absolute neutrophil count (ANC) >= 1,500/mcl obtained within 28 days prior to
sub-study registration
• Platelet count >= 100,000 mcl obtained within 28 days prior to sub-study registration
• Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study registration
• Serum bilirubin =< institutional upper limit of normal (IULN) within 28 days prior to
sub-study registration; for patients with liver metastases, bilirubin must be =< 5 x
IULN
• Either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 2 x IULN
within 28 days prior to sub-study registration (if both ALT and AST are done, both
must be =< 2 IULN); for patients with liver metastases, either ALT or AST must be =<
5 x IULN (if both ALT and AST are done, both must be =< 5 x IULN)
• Serum creatinine =< the IULN OR measured or calculated creatinine clearance >= 50
mL/min using the following Cockcroft-Gault Formula within 28 days prior to sub-study
registration
• Patients must have Zubrod performance status 0-1 documented within 28 days prior to
sub-study registration
• Patients must not have any grade III/IV cardiac disease as defined by the New York
Heart Association Criteria (i.e., patients with cardiac disease resulting in marked
limitation of physical activity or resulting in inability to carry on any physical
activity without discomfort), unstable angina pectoris, and myocardial infarction
within 6 months, or serious uncontrolled cardiac arrhythmia
• Patients must not have documented evidence of acute hepatitis or have an active or
uncontrolled infection
• Patients with a known history of human immunodeficiency virus (HIV) seropositivity
must: 1) have undetectable viral load using standard HIV assays in clinical practice,
2) have cluster of differentiation (CD)4 count >= 400/mcL, 3) not require prophylaxis
for any opportunistic infections (i.e., fungal, Mycobacterium avium complex [mAC], or
pneumocystis jiroveci pneumonia [PCP] prophylaxis), and 4) not be newly diagnosed
within 12 months prior to sub-study registration
• Prestudy history and physical exam must be obtained within 28 days prior to sub-study
registration
• No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
stage I or II cancer from which the patient is currently in complete remission, or
any other cancer from which the patient has been disease free for five years
• Patients must not be pregnant or nursing; women/men of reproductive potential must
have agreed to use an effective contraceptive method; a woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months; in addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures
• As part of the OPEN registration process the treating institution's identity is
provided in order to ensure that the current (within 365 days) date of institutional
review board approval for this study has been entered into the system
• Patients with impaired decision-making capacity are eligible as long as their
neurological or psychological condition does not preclude their safe participation in
the study (e.g., tracking pill consumption and reporting adverse events to the
investigator)
• Patients must be informed of the investigational nature of this study and must sign
and give written informed consent in accordance with institutional and federal
guidelines.

Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive RxPONDER Breast Cancer

Contact(s):
CTO@hmc.psu.edu

Gender:
Female

Age:
18 and over

Phase:
Phase 3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of node positive (1-3 nodes)
invasive breast carcinoma with positive estrogen and/or progesterone receptor status,
and negative HER-2 status; estrogen and progesterone receptor positivity must be
assessed according to American Society of Clinical Oncology (ASCO)/College of
American Pathologists (CAP) guidelines as either estrogen receptor (ER) or
progesterone receptor (PR) >= 1% positive nuclear staining; HER-2 test result
negativity must be assessed as per ASCO/CAP 2013 guidelines using
immunohistochemistry (IHC), in situ hybridization (ISH) or both; HER-2 is negative if
a single test (or all tests) performed in a tumor specimen show: a) IHC negative (0
or 1+) or b) ISH negative using single probe or dual probe (average HER-2 copy number
< 4.0 signals per cell by single probe or HER-2/CEP ration < 2.0 with an average copy
number < 4.0 signals per cell by dual probe); if HER-2 IHC is 2+, evaluation for gene
amplification (ISH) must be performed and the ISH must be negative; ISH is not
required if IHC is 0 or 1+; HER-2 equivocal is not eligible
• Patients with multifocal, multicentric and synchronous bilateral breast cancers are
allowed
• Multifocal disease is defined as more than one invasive cancer < 2 cm from the
largest lesion within the same breast quadrant; (NOTE: the Oncotype DX testing
must be completed on the largest lesion)
• Multicentric disease is defined as more than one invasive cancer >= 2 cm from
the largest lesion within the same breast quadrant or more than one lesion in
different quadrants (NOTE: Oncotype DX testing should be completed on all tumors
and the determination for eligibility should be made on the highest recurrence
score)
• Synchronous bilateral disease is defined as invasive breast cancer with positive
lymph nodes (axillary or intramammary) in at least one breast, diagnosed within
30 days of each other; (NOTE: the Oncotype DX testing should be completed on
both tumors and the tumor with the highest recurrence score should be used)
• Patients will have undergone axillary staging by sentinel node biopsy or axillary
lymph nodes dissection (ALND); patients must have at least one, but no more than
three known positive lymph nodes (pN1a, pN1b or pN1c); patients with micrometastases
as the only nodal involvement (pN1mi) are not eligible; patients with positive
sentinel node are not required to undergo full axillary lymph node dissection; this
is at the discretion of the treating physician; axillary node evaluation is to be
performed per the standard of care at each institution
• Patients must not have inflammatory breast cancer and must not have metastatic
disease
• Patients with a prior diagnosis of contralateral ductal carcinoma in situ (DCIS) are
eligible if they underwent a mastectomy or lumpectomy with whole breast radiation;
prior partial breast irradiation, including brachytherapy, is not allowed; patients
with a prior diagnosis of ipsilateral DCIS or invasive breast cancer who received
radiation to that breast are not eligible
• Patients must have had either breast-conserving surgery with planned radiation
therapy or total mastectomy (with or without planned postmastectomy radiation);
patients must have clear margins from both invasive breast cancer and DCIS (as per
local institutional guidelines); lobular carcinoma in situ (LCIS) at the margins is
allowed
• Registration of patients who have not yet undergone Oncotype DX screening must occur
no later than 56 days after definitive surgery; (for all patients, Step 2
Registration must occur within 84 days after definitive surgery); if the Oncotype DX
Breast Cancer Assay has not been performed, patients must be willing to submit tissue
samples for testing to determine the Recurrence Score value; a representative block
or unstained sections from the representative block are sent directly to Genomic
Health for Oncotype DX Breast Cancer Assay which will be performed according to the
standard commercial process
• If the Oncotype DX Recurrence Score is already known and is 25 or less, the
patient must be registered to Step 2 immediately following Step 1 registration;
if the Oncotype DX Recurrence Score is already known and is greater than 25, the
patient is ineligible
• Patients must have a complete history and physical examination within 28 days prior
to registration
• Patients must have a performance status of 0-2 by Zubrod criteria
• Patients must be able to receive taxane and/or anthracycline based chemotherapy
• Patients must not have begun chemotherapy or endocrine therapy for their breast
cancer prior to registration
• Patients must not require chronic treatment with systemic steroids (inhaled steroids
are allowed) or other immunosuppressive agents
• Patients must not have received an aromatase inhibitor (AI) or a selective estrogen
receptor modulator (SERM) such as tamoxifen or raloxifene within 5 years prior to
registration
• Patients must not be pregnant or nursing; women of reproductive potential must have
agreed to use an effective contraceptive method; a woman is considered to be of
"reproductive potential" if she has had menses at any time in the preceding 12
consecutive months; in addition to routine contraceptive methods, "effective
contraception" also includes heterosexual celibacy and surgery intended to prevent
pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
previously celibate patient chooses to become heterosexually active during the time
period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures
• No other prior malignancy is allowed except for adequately treated basal cell (or
squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the
patient has been disease-free for 5 years
• The Quality of Life and Economic Substudy is permanently closed to accrual effective
12/1/12; patients who consented to QOL prior to 12/1/12 should continue to complete
QOL forms per their expectation report; patients who are able to complete a
questionnaire in English must be offered the opportunity to participate in the
Quality of Life and Economic Substudy; (The Quality of Life and Economic Substudy is
available to U.S. INSTITUTIONS ONLY); patients who are not able to complete a
questionnaire in English are registered to S1007 without participating in the Quality
of Life and Economic Substudy
• Patients who consent to participate in the Quality of Life and Economic Substudy
and who do not yet know the results of their Oncotype DX screening must agree to
complete the S1007 Health-Related Quality of Life Questionnaire: Enrollment
between 14 days prior to and 7 days after Step 1 Registration
• Patients who consent to participate in the Quality of Life and Economic Substudy
and who do already know their Oncotype DX Recurrence Score (and it is 25 or
less) will proceed to Step 2 Registration without completing the S1007
Health-Related Quality of Life Questionnaire Enrollment Form (but will complete
the S1007 Health-Related Quality of Life Questionnaire: Randomized Study Form)
• Patients or their legally authorized representative must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines; for Step 1 registration of
patients who have not yet submitted specimens for the Oncotype DX Breast Cancer
Assay, the appropriate consent form is the Step 1 Consent Form; for both Step 1 and
Step 2 registration of patients whose Recurrence Score is already known and is 25 or
less, the appropriate consent form is the Step 2 Consent Form
• As a part of the Oncology Patient Enrollment Network (OPEN) registration process the
treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
• STEP 2 REGISTRATION
• Recurrence score (RS) by Oncotype DX must be =< 25
• Step 2 Registration must take place within 84 days after definitive surgery; patients
must not have begun chemotherapy or endocrine therapy for their breast cancer prior
to randomization
• Patients randomized to either arm may also co-enroll in phase III trials that compare
local therapies, or compare systemic therapies (such as chemotherapy, if randomized
to Arm I of S1007)
• The Quality of Life and Economic Substudy is permanently closed to accrual effective
12/1/12; patients at U.S. INSTITUTIONS who consent to participate in the Quality of
Life and Economic Substudy must agree to complete the S1007 Health-Related Quality of
Life Questionnaire: Randomized Study Form after Recurrence Score results and
randomized treatment status are known but before treatment has been initiated
• Patients or their legally authorized representative must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines; for all patients the
appropriate consent form for this registration is the Step 2 Consent

DISEASE CHARACTERISTICS:
• Histologically confirmed adenocarcinoma of the breast
• Stage III (locally advanced), metastatic, or recurrent disease
• Deemed not resectable
• Estrogen-receptor and/or progesterone-receptor positive disease
• Receptor status is based on most recent results
• Receptor testing on metastatic disease is not required
• Measurable or non-measurable disease
• History of CNS metastasis allowed provided it has been treated (surgery,
radiotherapy, or radiosurgery) within the past 4 weeks and does not require
medications to control symptoms
• No known leptomeningeal disease allowed
PATIENT CHARACTERISTICS:
• ECOG performance status 0-2
• Menopausal status not specified
• Total bilirubin = 1.5 times upper limit of normal (ULN)
• ALT and AST = 2.5 times ULN (= 5 times ULN if liver metastases present)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No medical or psychiatric conditions that would interfere with protocol compliance,
the ability to provide informed consent, assessment of response, or anticipated
toxicities
• More than 5 years since prior invasive malignancies except curatively treated basal
cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
• See Disease Characteristics
• No prior investigational agents in the metastatic setting
• Other prior investigational agents in any setting must have been completed at
least 6 weeks prior to study registration and should be discussed with the study
PI
• Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have
disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last
dose
• Prior tamoxifen for advanced disease is not allowed
• No prior chemotherapy or trastuzumab (Herceptin) for metastatic disease
• Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed
provided it has been completed = 4 weeks before study therapy
• Patients must not have had more than 2 lines of non-hormonal treatment in the locally
advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or
other biologics
• Treatment in the advanced setting must have been completed at least 2 weeks
prior to study initiation
• Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane,
aminoglutethamide) are allowed in the adjuvant or metastatic setting
• At least 2 weeks since prior and no concurrent medications that are strong to
moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including,
but not limited to, any of the following:
• Paroxetine (Paxil)
• Fluoxetine (Prozac)
• Bupropion (Wellbutrin)
• Quinidine (Cardioquin)
• Patients may not initiate bisphosphonate therapy while receiving treatment on this
study
• Patients who have begun receiving bisphosphonate therapy prior to registration
may continue at the same intervals used prior to study registration
• Concurrent radiotherapy to painful sites of bone disease or areas of impending
fractures allowed provided the following criteria are met:
• Radiotherapy was initiated before study entry
• Sites of measurable or non-measurable disease are outside the radiotherapy port
• Recovered from prior radiotherapy
• No other concurrent hormonal therapy
• No concurrent chemotherapy

• Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma
(SMM) within the past 60 months, as confirmed by both of the following:
• Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells at
any time before initiating study treatment, including a marrow which must be
obtained by bone marrow aspiration and/or biopsy within 4 weeks prior to
randomization
• Abnormal serum free light chain ratio (< 0.26 or > 1.65) by serum free light
chain (FLC) assay; FLC assay must be performed within 28 days of randomization
• Patients must have measurable levels of monoclonal protein (M-protein): >= 1g/dL on
serum protein electrophoresis or >= 200 mg of monoclonal protein on a 24 hour urine
protein electrophoresis which must be obtained within 4 weeks prior to randomization
• Patients must have no lytic lesions on skeletal surveys and no hypercalcemia (i.e.,
>= 11 mg/dL)
• Hemoglobin >= 11 g/dL
• Platelet count >= 100,000/mm^3
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Calculated creatinine clearance >= 30 mL/min
• Bilirubin =< 1.5 mg/dL
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and
serum glutamic oxaloacetic transaminase (SGPT) (aspartate aminotransferase [AST]) =<
2.5 times upper limit of normal
• No prior or concurrent systemic or radiation therapy for the treatment of myeloma
• Concurrent use of bisphosphonates is not permitted; however, prior bisphosphonates or
once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is
permitted
• Prior or concurrent use of erythropoietin is disallowed
• Prior glucocorticosteroid therapy for the treatment of multiple myeloma is not
permitted
• Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders
is permitted; concurrent use after registration on the study should be restricted to
the equivalent of prednisone 10 mg per day
• Prior or concurrent topical or localized glucocorticosteroid therapy to treat
non-malignant comorbid disorders is permitted
• Patients must not have active, uncontrolled seizure disorder; patients must have had
no seizures in the last 6 months
• Patients must not have uncontrolled intercurrent illness including uncontrolled
hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled
cardiac arrhythmia, uncontrolled psychiatric illness or social situation that would
limit compliance with the study, or a prior history of Stevens Johnson syndrome
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Patients must not have baseline bone lesions or plasmacytomas
• Patients with monoclonal gammopathy of undetermined significance are not eligible
• Patients must not have grade 2 or higher peripheral neuropathy
• Patients must not have active, uncontrolled infection
• Patients may have a history of current or previous deep vein thrombosis or pulmonary
embolism but are required to take some form of anti-coagulation as prophylaxis if
they are not currently on full-dose anticoagulation
• Patients should not have New York Heart Association classification III or IV heart
failure
• Patients with a history of prior malignancy are eligible provided they were treated
with curative intent and have been free of disease for the time period considered
appropriate for cure of the specific cancer; for most diseases this time frame is 5
years
• Patients should not be felt to have an immediate need for chemotherapy
• Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 10 •14 days prior to
and again within 24 hours of starting cycle 1 of lenalidomide and must either commit
to continued abstinence from heterosexual intercourse or begin TWO acceptable methods
of birth control, one highly effective method and one additional effective method AT
THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also
agree to ongoing pregnancy testing; men must agree to use a latex condom during
sexual contact with a FCBP even if they have had a successful vasectomy; a FCBP is a
sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
months (i.e., has had menses at any time in the preceding 24 consecutive months); all
patients must be counseled by a trained counselor every 28 days about pregnancy
precautions and risks of fetal exposure
• Human immunodeficiency virus (HIV) infection is not excluded; HIV+ patients must meet
the following criteria:
• Cluster of differentiation (CD)4 cell count >= 350/mm^3
• No history of acquired immune deficiency syndrome (AIDS)-related illness
• Not currently prescribed zidovudine or stavudine

Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer

Contact(s):
CTO@hmc.psu.edu

Gender:
Male

Age:
18 and over

Phase:
Phase 3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

DISEASE CHARACTERISTICS:
• Histologically confirmed adenocarcinoma of the prostate diagnosed within the past 180
days and at intermediate-risk for recurrence by meeting 1 or more of the following
criteria:
• Gleason score = 7
• Prostate Specific Antigen (PSA) > 10 and = 20 ng/mL
• Baseline serum PSA value performed within 60 days with an FDA-approved
assay (e.g., Abbott, Hybritech)
• Baseline PSA must not be obtained during any of the following time
frames:10-day period after prostate biopsy, after initiation of
androgen-deprivation therapy, or within the past 30 days after
discontinuation of finasteride (90 days for dutasteride)
• Clinical stage T2b or T2c disease
• Patients previously diagnosed with low-risk (Gleason score < 6, clinical stage <
T2a, and PSA < 10 ng/mL) prostate cancer undergoing active surveillance who are
re-biopsied and found to have intermediate-risk disease according to the
protocol criteria are eligible for enrollment within 6 months of the repeat
biopsy procedure
• Patients with Gleason Score = 8, PSA > 20 ng/mL, OR clinical stage = T3 are
ineligible for this trial
• If findings of extracapsular extension or seminal vesicle invasion are noted on
prostate MRI, this study, if used, will not render patients ineligible for
accrual to this protocol
• Primary tumor staging for eligibility purposes is to be based on palpable or
core biopsy evidence only with respect to extracapsular extension or seminal
vesicle involvement
• No patients with all 3 intermediate-risk factors who also have = 50% of the number of
their biopsy cores positive for cancer
• The percentage of biopsy cores involved will only be considered with respect to
eligibility for those patients with all 3 of the above risk factors (i.e.,
patients with one or two of the above risk factors are eligible irrespective of
the percentage of biopsy cores involved)
• Clinically negative lymph nodes as established by imaging (pelvic and/or abdominal CT
scan or MRI), nodal sampling, or dissection within the past 60 days (required for
patients with 2-3 risk factors)
• Abdominal imaging not required for a single intermediate-risk factor (these
studies may be obtained at the discretion of the treating physician)
• Lymph nodes that are equivocal or questionable by imaging allowed without biopsy
if nodes = 1.5 cm
• Any node > 1.5 cm on imaging requires a negative biopsy
• No evidence of bone metastases on bone scan within the past 60 days
• Bone scan not required for patients with a single intermediate-risk factor (scan
may be obtained at the discretion of the treating physician)
• Equivocal bone scan findings allowed if plain film x-rays negative for
metastasis
PATIENT CHARACTERISTICS:
• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) = 1,800/mm^3*
• Platelet count = 100,000/mm^3*
• Hemoglobin = 8.0 g/dL (transfusion or other intervention to achieve level allowed)*
• NOTE: *For patients undergoing brachytherapy only.
• Fertile patients must use effective contraception during and for the 3 months after
cessation of protocol treatment
• No invasive malignancy or hematological malignancy (e.g., leukemia, lymphoma,
myeloma) within the past 5 years except adequately treated non-melanomatous skin
cancer
• Prior diagnoses of carcinoma in situ allowed
• No severe or active co-morbidity with any of the following:
• Unstable angina and/or congestive heart failure requiring hospitalization within
the past 6 months
• Transmural myocardial infarction within the past 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy, within the past 30 days
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Laboratory tests for liver function and coagulation parameters not required
for entry into this protocol
• AIDS based upon current Centers for Disease Control (CDC) definition
• HIV testing not required for entry into this protocol
• HIV-seropositive patients who do not meet criteria for diagnosis of AIDS
allowed
PRIOR CONCURRENT THERAPY:
• See Disease Characteristics
• No prior radical surgery (prostatectomy), high-intensity focused ultrasound, or
cryosurgery for prostate cancer
• No prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide),
antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or bilateral
orchiectomy
• No finasteride within past 30 days (90 days for dutasteride)
• No prior or concurrent cytotoxic chemotherapy for prostate cancer
• Prior chemotherapy for a different cancer allowed
• No prior radiotherapy (RT), including brachytherapy, to the region of the study
cancer that would result in overlap of RT fields
• Patients undergoing brachytherapy must have transrectal ultrasound confirmation
of prostate volume < 60 cc, American Urological Association (AUA) score = 15
within the past 60 days of registration, and no history of prior transurethral
resection of the prostate (TURP)
• TURP allowed for patients who receive external-beam radiation therapy only

Lenalidomide With or Without Epoetin Alfa in Treating Patients With Myelodysplastic Syndrome and Anemia

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
18 and over

Phase:
Phase 3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• NOTE: Results of the bone marrow biopsy and aspirate as well as cytogenetics are
mandatory to register subjects onto study, which are indispensable to determine
International Prognostic Scoring System (IPSS) category needed for eligibility;
please note that it is not necessary to wait for the week 16, week 32, or week bone
marrow and cytogenetic results prior to starting the next cycle unless deemed
necessary by the treating physician; one example of this exception can include if the
subject shows signs of progression, such as increased peripheral blood blast
percentage; at that juncture, the treating physician may prefer to await the results
prior to starting a new cycle; if a cycle is started, and based on the bone marrow
results it is felt by the treating physician that the subject should not continue on
treatment, please be sure to note this information on the case report forms at end of
treatment
• Patient must have documented diagnosis of MDS lasting at least three months (MDS
duration >= 3 months) according to World Health Organization (WHO) criteria or
non-proliferative chronic myelomonocytic leukemia (CMML) (white blood cell [WBC] <
12,000/mcL)
• Patient must have IPSS categories of low- or intermediate-1-risk disease; patients
must have IPSS score determined by cytogenetic analysis prior to randomization;
patients must have cytogenetic analysis done (to calculate IPSS); if the current bone
marrow biopsy is a dry tap, patients with cytogenetic failure and < 10% marrow blasts
will be eligible; subjects with cytogenetic failure must have previous cytogenetic
results (fluorescence in situ hybridization [FISH] is not a substitute) within the
last 6 months post last type of MDS treatment (in this case, not referring to growth
factors as type of MDS treatment)
• Must have symptomatic anemia untransfused with hemoglobin < 9.5 g/dL =< 8 weeks prior
to randomization or with red blood cells (RBC) transfusion dependence (i.e., >= 2
units/month) confirmed for =< 8 weeks before randomization
• NOTE: For non-transfusion dependent patients (i.e., receiving < 2 units/4 weeks
x 8 weeks pre-study) who receive periodic transfusions, the mean 8 week
pre-transfusion hemoglobin should be used to determine protocol eligibility and
response reference
• For non-transfusion dependent patients, a minimum of 2 pre-transfusion or
un-transfused hemoglobin values are required
• Applies only for patients without the deletion 5q 31.1; patients must have failed
treatment with an erythropoietic growth factor, or have a low probability of response
to rhu-erythropoietin; patients with low probability of response to
rhu-erythropoietin or prior erythropoietin failures are defined as follows:
• Prior erythropoietin failure-requires a minimum trial of >= 40,000 units epoetin
alfa/week x 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks with
failure to achieve transfusion independence in dependent patients or a failure
to achieve a >= 2 g rise in hemoglobin sustained for >= 4 weeks in
non-transfusion dependent patients
• Low erythropoietin response profile-rhu-erythropoietin and epoetin alfa-naïve
patients receiving >= 2U packed (p)RBC/month for a minimum of 8 weeks, and serum
erythropoietin > 500 mU/mL in the 8 weeks prior to randomization for a
hemoglobin < 9.5 g/dL
• Patients must be off all non-transfusion therapy for MDS for 28 days prior to
initiation of study treatment, including all types of growth factors; patients may
receive hydrocortisone prophylactically to prevent transfusion reactions
• Patients must have a serum erythropoietin level documented before randomization and
=< 56 days before day 1 of study treatment; NOTE: hemoglobin must be < 9.5 g/dL at
time that serum erythropoietin is drawn
• Patients must not have documented iron deficiency; all patients must have documented
marrow iron stores; if marrow iron stain is not available, the transferrin saturation
must be > 20% or a serum ferritin > 100 ng/mL
• Women must not be pregnant or breastfeeding; females of childbearing potential must
have a negative serum or urine pregnancy test with a sensitivity of at least 25
mIU/mL within 10-14 days and again within 24 hours prior to starting cycle 1 of
lenalidomide; a female of childbearing potential (FCBP) is any woman, regardless of
sexual orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or
2) has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months; FCBP must also
agree to ongoing pregnancy testing)
• Effective contraception must be used by patients participating in lenalidomide
therapy, and all patients must agree to counseling by a trained counselor every 28
days about pregnancy precautions and risks of fetal exposure; females of childbearing
potential (FCBP) must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control: one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
starting lenalidomide, during lenalidomide therapy, during dose interruptions, and
for at least 28 days following discontinuation of lenalidomide therapy; females of
childbearing potential should be referred to a qualified provider of contraceptive
methods, if needed; males receiving lenalidomide must agree to use a latex condom
during any sexual contact with females of childbearing potential even if they have
undergone a successful vasectomy
• Patients must not have prior therapy with lenalidomide
• Patients must not have a diagnosis of uncontrolled seizure or uncontrolled
hypertension
• Patients must not have proliferative (WBC >= 12,000/mcL) chronic myelomonocytic
leukemia (CMML); WBC must be < 12,000/mcL
• Patients must not have MDS secondary to treatment with radiotherapy, chemotherapy,
and/or immunotherapy for malignant or autoimmune diseases
• Platelet count >= 50,000/mcL (50 x 10^9/L) without platelet transfusion
• Absolute neutrophil count (ANC) >= 500 cells/mcL (0.5 x 10^9/L); hence ANC must be >=
500/mcL without myeloid growth factor support
• Serum creatinine =< 1.5 times upper limit of normal (ULN)
• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or
serum glutamate pyruvate transaminase (SGPT)/alanine aminotransferase (ALT) =< 2.0 x
ULN
• Serum total bilirubin < 3.0 mg/dL
• Prior thalidomide is allowed, however, patients must not have prior >= grade-3
allergic reactions to thalidomide
• Patients must not have prior history of desquamating rash from thalidomide at time of
study entry
• Patients must not have clinically significant anemia resulting from iron, B12 or
folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
• Patients must not have used cytotoxic chemotherapeutic agents or experimental agents
(agents that are not commercially available) for the treatment of MDS within 8 weeks
of randomization
• Patients must not have prior history of malignancy other than MDS (except basal cell
or squamous skin cell carcinoma or carcinoma in situ of the cervix or breast) unless
the subject has been confirmed free of disease for >= 3 years
• Patients must not have any serious medical condition or any other unstable medical
co-morbidity, or psychiatric illness that will prevent the subject from signing the
informed consent form or will place the subject at unacceptable risk if he/she
participates in the study
• Patients must not have a history of thrombo-embolic events within 3 years prior to
study randomization
• Patients must not have known human immunodeficiency virus (HIV)-1 seropositivity
• Patients must not have a known allergic reaction to epoetin alfa (Procrit) or human
serum albumin
• Eligibility for crossover registration from Arm A (lenalidomide alone) to Arm B
(lenalidomide and epoetin alfa):
• Patients must have completed 16 weeks of monotherapy with lenalidomide
• Patients must show failure to achieve MER (major erythroid response) or have achieved
MER but relapsed on Arm A
• Patients must not have a limiting unresolved grade 3 or greater toxicity from
lenalidomide monotherapy or drug intolerance preventing continuation of lenalidomide
treatment

Study of Ataluren in Nonsense Mutation Cystic Fibrosis (ACT CF)

Contact(s):
CTO@hmc.psu.edu

Gender:
Male or Female

Age:
6 and over

Phase:
Phase 3

Healthy Volunteers:

This study is NOT accepting healthy volunteers

Hide eligibility criteria

Inclusion Criteria:

• Evidence of signed and dated informed consent/assent document(s) indicating that the
subject (and/or his parent/legal guardian) has been informed of all pertinent aspects
of the trial
• Age >=6 years.
• Body weight >=16 kg.
• Sweat chloride >60 mEq/L
• Documentation of the presence of a nonsense mutation in at least 1 allele of the CFTR
gene, as determined by genotyping performed at a laboratory certified by the College
of American Pathologists (CAP), or under the Clinical Laboratory Improvement
Act/Amendment (CLIA), or by an equivalent organization
• Verification that a blood sample has been drawn for sequencing of the CFTR gene
• Ability to perform a valid, reproducible spirometry test using the study-specific
spirometer with demonstration of an FEV1 >=40% and <=90% of predicted
• Demonstration at Visit 2 of a valid %-predicted FEV1 within 15% of the Screening %
predicted FEV1 value
• Resting oxygen saturation (as measured by pulse oximetry) >=92% on room air.
• Confirmed screening laboratory values within pre-specified ranges
• In subjects who are sexually active, willingness to abstain from sexual intercourse
or employ a barrier or medical method of contraception during the study drug
administration and 60-day follow-up period
• Willingness and ability to comply with all study procedures and assessments,
including scheduled visits, drug administration plan, study procedures, laboratory
tests, and study restrictions

Exclusion Criteria:

• Known hypersensitivity to any of the ingredients or excipients of the study drug
• Previous participation in the Phase 3 trial of ataluren (PTC124-GD-009-CF).
• Any change (initiation, change in type of drug, dose modification, schedule
modification, interruption, discontinuation, or re-initiation) in a chronic
treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks
prior to screening
• Chronic use of inhaled aminoglycosides (eg, tobramycin) or use of inhaled
aminoglycosides within 4 months prior to screening.
• Exposure to another investigational drug within 4 weeks prior to screening
• Ongoing participation in any other therapeutic clinical trial
• Evidence of pulmonary exacerbation or acute upper or lower respiratory tract
infection (including viral illnesses) within 3 weeks prior to screening
• Treatment with intravenous antibiotics within 3 weeks prior to screening
• Ongoing immunosuppressive therapy (other than corticosteroids)
• Ongoing warfarin, phenytoin, or tolbutamide therapy
• History of solid organ or hematological transplantation
• Major complications of lung disease (including massive hemoptysis, pneumothorax, or
pleural effusion) within 8 weeks prior to screening
• Known portal hypertension
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human
immunodeficiency virus (HIV) test
• Pregnancy or breast-feeding
• Current smoker or a smoking history of >=10 pack-years (number of cigarette packs/day
x number of years smoked).
• Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse,
psychiatric condition), medical history, physical findings, ECG findings, or
laboratory abnormality that, in the investigator's opinion, could adversely affect
the safety of the subject, makes it unlikely that the course of treatment or
follow-up would be completed, or could impair the assessment of study results